Cardiovascular depressant effects of N-methyl- and N-isobutyl-1,2-diphenyl ethanolamines: elucidation of the mechanisms of action.
Arch Int Pharmacodyn Ther
; 309: 88-102, 1991.
Article
in En
| MEDLINE
| ID: mdl-1888233
ABSTRACT
The cardiovascular effects of N-methyl-1,2-diphenyl ethanolamine (compound M) and N-isobutyl-1,2-diphenyl ethanolamine (compound E) were examined in anaesthetized rats and their effects were compared with those of verapamil and diltiazem. Administration of compound M (10-80 mumole/kg), compound E (2-16 mumole/kg), diltiazem (1.5-24 mumole/kg) or verapamil (1.25-10 mumole/kg) induced dose-dependent decreases in arterial blood pressure and heart rate. The induced cardiovascular changes were not antagonized by chlorpheniramine, cimetidine or imidazole. Indomethacin antagonized the diltiazem-induced hypotension without any effect on that of compounds M and E. The effects of all compounds tested were antagonized by pretreatment of the rats with CaCl2 (1.2-2.4 mmole/kg). Furthermore, methylene blue significantly antagonized the compound E- and diltiazem-induced hypotension. Treatment of the animals with propranolol enhanced the compound M- and E-induced hypotension. Compounds M and E antagonized the NA-induced increase in arterial blood pressure in a competitive manner. Compounds M and E seem to exert their cardiovascular effects via interference with the influx of extracellular Ca2+. Furthermore, compound E and diltiazem may act partially via activation of guanylyl cyclase.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ethanolamines
/
Anti-Arrhythmia Agents
Limits:
Animals
Language:
En
Journal:
Arch Int Pharmacodyn Ther
Year:
1991
Document type:
Article